Immunsuppression und Infektionsprophylaxe nach Lungentransplantation

Zusammenfassung

Die Lungentransplantation (LTX) ist ein etabliertes Therapieverfahren für Lungenerkrankungen im Endstadium. Hauptursachen für die unbefriedigenden Langzeitüberlebensraten sind Infektionen und das Bronchiolitis-obliterans-Syndrom (BOS). Für beide Komplikationen spielt eine optimale immunsuppressive Strategie eine entscheidende Rolle. Über 60 % der Organempfänger erhalten eine Induktionstherapie, ohne dass bisher ein signifikanter Vorteil bezüglich Langzeitüberleben in kontrollierten Studien demonstriert wurde. Die große Mehrheit der Patienten wird lebenslang mit einer dreifach immunsuppressiven Erhaltungstherapie, bestehend aus einem Calcineurin-Inhibitor, einem Zellzyklus-Inhibitor und einem oralen Kortikosteroid, behandelt. Eine eindeutige Überlegenheit in Bezug auf Langzeitüberleben konnte bisher jedoch für keine der spezifischen Immunsuppressiva-Kombination gezeigt werden. Ob die neueren Proliferations-Signal-Inhibitoren Sirolimus und Everolimus signifikante Vorteile bieten, ist noch nicht abschließend zu beurteilen. Zur Therapie des BOS werden eine Umstellung der Erhaltungstherapie, eine erneute Induktionstherapie, inhalatives Cyclosporin A sowie u. a. Azithromyzin, extrakorporale Photopherese und Lymphsystembestrahlung angewendet. Die Infektionsprophylaxe nach LTX spielt eine entscheidende Rolle bei der Vermeidung von akuten Komplikationen und auch in der Verhinderung des BOS. Insbesondere zur Prophylaxe einer Pneumocystis- und Cytomegalievirus-Erkrankung stehen effektive medikamentöse Optionen zur Verfügung. Darüber hinaus wurde auch die Kolonisierung mit Pseudomonas aeruginosa und Aspergillus-Spezies als Risikofaktor für BOS erkannt. Entsprechende prophylaktische bzw. prä-emptive Therapieansätze finden daher in unterschiedlichem Ausmaß in den meisten Transplantationszentren Anwendung.

Abstract

Lung transplantation (LTX) is an established therapeutic option for end-stage lung diseases. The main reasons for limited long-term survival rates are infections and bronchiolitis obliterans syndrome (BOS). An optimal immunosuppressive regimen is of critical importance for the prevention of both complications. Induction therapy is used in approximately 60 % of recipients. However, there are no controlled trials demonstrating a significant long-term survival benefit. The vast majority of patients receive a triple maintenance immunosuppressive therapy consisting of a calcineurin-inhibitor, a cell cycle inhibitor and corticosteroids. So far, no specific immunosuppressive drug combination has proven superiority regarding long-term survival rates. The potential benefits of the proliferation signal inhibitors sirolimus and everolimus remain to be elucidated. Therapeutic options for BOS encompass a switch in maintenance therapy, renewed induction therapy, aerolised cyclosporine, azithromycine, extracorporeal photopheresis and total lymphoid irradiation. Infection prophylaxis after LTX plays a pivotal role to guard against acute complications and for the prevention of BOS. In particular, prophylaxis for pneumocystis and cytomegalovirus disease is very effective. Moreover, colonisation with Pseudomonas aeruginosa and Aspergillus spp. was identified as risk factor for BOS. Consequently, in most transplant centres prophylactic and pre-emptive therapeutic approaches are applied in varying degrees.

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